THOUSAND OAKS, Calif. and LONDON—Amgen and AstraZeneca recently announced that the Phase 3 AMAGINE-1 study evaluating brodalumab in patients with moderate to severe plaque psoriasis met all primary and secondary endpoints for both evaluated doses. Brodalumab is reportedly the only investigational treatment in development that binds to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling by blocking the binding of several IL-17 ligands to the receptor.
Specifically, the primary endpoints were considered to be patients achieving at least a 75 percent improvement from baseline in disease severity at week 12, as measured by the Psoriasis Area Severity Index (PASI 75), and patients achieving clear or almost clear skin at week 12 according to the static Physician Global Assessment (sPGA 0 or 1).
A significantly higher proportion of patients treated with brodalumab achieved a PASI 75 response, as well as PASI 90 and PASI 100 responses at week 12 compared to placebo, according to the companies. Results showed that 83.3 percent of patients in the 210 mg group and 60.3 percent of patients in the 140 mg group achieved PASI 75 responses compared to placebo (2.7 percent). Results also showed that 70.3 percent of patients in the 210 mg group and 42.5 percent of patients in the 140 mg group achieved PASI 90 responses compared to placebo (0.9 percent). Further, 41.9 percent of patients in the 210 mg group and 23.3 percent of patients in the 140 mg group achieved PASI 100 responses compared to placebo (0.5 percent).
The most common adverse events that occurred during the placebo-controlled period in the brodalumab group (more than 5 percent of participants) were nasopharyngitis, upper respiratory tract infection and headache. Serious adverse events occurred in 1.8 percent of patients in the 210 mg group and 2.7 percent of patients in the 140 mg group compared to 1.4 percent for placebo during the placebo-controlled period.
“Data from the AMAGINE-1 study suggest that brodalumab may offer a new level of efficacy for patients with moderate to severe plaque psoriasis, a disease that affects more than 100 million people globally,” according to Dr. Sean E. Harper, executive vice president of research and development at Amgen. “This is the first readout from our Phase 3 psoriasis clinical program, and we look forward to obtaining additional Phase 3 data from our two head-to-head studies versus ustekinumab later this year.”
Psoriasis is a non-contagious chronic disease in which the immune system causes skin cells to grow at an accelerated rate. Instead of being shed, skin cells pile up, causing painful, itchy, red, scaly patches.
“Moderate to severe plaque psoriasis is a serious disease, and despite available treatments, there is still a significant need for more effective therapies,” according to Dr. Briggs W. Morrison, executive vice president of global medicines development at AstraZeneca. “We are encouraged by brodalumab’s emerging profile and look forward to presenting the full data in the appropriate scientific forum.”
AMAGINE-1 is one of three Phase 3 studies designed to assess the efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis. AMAGINE-2 and AMAGINE-3 are designed to evaluate the efficacy and safety of induction and maintenance regimens of brodalumab at different dose schedules in patients with moderate to severe plaque psoriasis compared to ustekinumab and placebo.
The Phase 3 data on brodalumab is “encouraging for both Amgen and AstraZeneca,” according to Zacks Investment Research. “These results bring Amgen and AstraZeneca a step closer to regulatory filing, though two more Phase 3 studies are still ongoing—AMAGINE-2 and AMAGINE-3 … Both companies are working on strengthening their product portfolio and brodalumab is one of the key candidates in their pipeline.”
However, while Zacks acknowledged analyst estimates for brodalumab’s revenue potential at between $500 million and $1.5 billion per year, it also noted that “the psoriasis market is highly crowded with treatments like Stelara and Otezla, among others. Moreover, several companies have late-stage candidates in development for the psoriasis market.”
In April 2012, Amgen and AstraZeneca formed a collaboration to jointly develop and commercialize five monoclonal antibodies from Amgen’s clinical inflammation portfolio. With oversight from joint governing bodies, Amgen leads clinical development and commercialization for brodalumab (Phase 3 for moderate to severe plaque psoriasis and psoriatic arthritis, Phase 2 for asthma) and AMG 557/MEDI5872 (Phase 1b for autoimmune diseases such as systemic lupus erythematosus). AstraZeneca, through its biologics arm MedImmune, leads clinical development and commercialization for MEDI7183/AMG 181 (Phase 2 for ulcerative colitis and Crohn’s disease), MEDI2070/AMG 139 (Phase 2 for Crohn's disease) and MEDI9929/AMG 157 (Phase 2 for asthma).